Ansh Malhotra
Research Mentor: Elizabeth Litkowski
Mentor Department: Neurology, Medicine
Author(s): Ansh Malhotra, Elizabeth Litkowski
Session: Session 4 (1:00 PM – 1:50 PM)
Presentation Type: Poster 59
Abstract
Aging is the primary risk factor for neurodegenerative diseases such as Alzheimer’s disease (AD), yet individual differences in cognitive decline imply that genetics is a likely factor. This study examines the role of the gene Prdm10 in the regulation of glucose metabolism and its impact on cognition using the AD-BXD genetically diverse mouse panel. Preliminary studies on 39 strains of the AD-BXD panel revealed that individual differences in glucose metabolism predicted memory performance. This study now examines how the role of the Prdm10 gene modifies cognition in the presence of the 5XFAD transgene known to cause Alzheimer’s disease pathology in mice. To study this mechanism, Prdm10 heterozygous knockout mice were created via CRISPR/Cas9 gene editing. Both a standard diet and a High Fat High Sucrose (HFHS) diet were initiated in Prdm10 knockout mice at the age of 2.5 months. This study evaluates cognitive function in 6 and 14-month-old mice using the Object Location Memory (OLM) assay, and metabolic function using Glucose Tolerance Tests. We found that a partial knockout of Prdm10 in 5XFAD mice significantly decreased the Object Location Memory (OLM) Discrimination Index (~0.05) compared to AD mice with normal Prdm10 expression (~0.11) and wild-type controls (~0.13), suggesting that Prdm10 plays a critical role in cognitive function, particularly in spatial memory. Future cohorts will help to determine how Prdm10 interacts with diet-induced metabolic function to impact cognitive resilience and how this information can be used in the future.
